It was supposed to prevent blindness and death
from vitamin A deficiency in millions of
children. But almost a decade after its
invention, golden rice is still stuck in the lab

It's easy to recognize Ingo Potrykus at the train
station in Basel, Switzerland. Quietly waiting
while hurried travelers zip by, he is holding, as
he promised, the framed and slightly yellowed
cover of the 31 July 2000 issue of Time magazine.
It features Potrykus's bearded face flanked by
some bright green stalks and a bold headline:"This Rice Could Save A Million Kids A Year."

The story ran at a time when Potrykus, a German
plant biotechnologist who has long lived in
Switzerland, was on a roll. In 1999, just as he
was about to retire, Potrykus and his colleagues
had stunned plant scientists and biotechnology
opponents alike by creating a rice variety that
produced a group of molecules called pro-vitamin
A in its seeds. The researchers thought this"golden rice"--named for the yellow hue imparted
by the compounds--held a revolutionary promise to
fight vitamin A deficiency, which blinds or kills
thousands of children in developing countries
every year.

Almost a decade later, golden rice is still just
that: a promise. Well-organized opposition and a
thicket of regulations on transgenic crops have
prevented the plant from appearing on Asian farms
within 2 to 3 years, as Potrykus and his
colleagues once predicted. In fact, the first
field trial of golden rice in Asia started only
this month. Its potential to prevent the ravages
of vitamin A deficiency has yet to be tested, and
even by the most optimistic projections, no
farmer will plant the rice before 2011.

The delays have made Potrykus, who lives in
Magden, a small village in an idyllic valley near
Basel, a frustrated man. For working on what he
considers a philanthropic project, he has been
ridiculed and vilified as an industry shill.
Relating the golden rice saga at his dinner table
while his wife serves croissants and strong
coffee, he at times comes off as bitter.

There's more at stake than golden rice and
personal vindication, he says. In his view, 2
decades of fear-mongering by organizations such
as Greenpeace, his prime nemesis, have created a
regulatory climate so burdensome that only big
companies with deep pockets can afford to get any
genetically modified (GM) product approved. As a
result, it has become virtually impossible to use
the technology in the service of the poor,
Potrykus says.
Not everybody is so gloomy. Potrykus's
co-inventor and main partner, plant biochemist
Peter Beyer of the University of Freiburg in
Germany, agrees that it's been a difficult
decade. But a more cheerful character by nature,
Beyer believes rules are just something to be
dealt with; complaining about them does little,
he says. A handful of other researchers working
on GM crops to fight malnutrition also feel
confident that their work will eventually pay off.

Many scientists agree with Potrykus, however,
that GM technology has become so controversial
that for now, there's little point in harnessing
it for the world's poorest. HarvestPlus, a vast
global program at public research institutes
aimed at creating more nutritious staple crops,
is forgoing GM technology almost entirely and
using conventional breeding instead, despite its
built-in limitations. GM products just might end
up on the shelf, says HarvestPlus Director
Howarth Bouis.

Potrykus, now 75 years old, worries that he may
not live to see his invention do any good. "It's
difficult for me not to get upset about this
situation," he says.

The idea for golden rice was born at an
international agricultural meeting in the
Philippines in 1984, says Gary Toenniessen of the
Rockefeller Foundation, a philanthropy in New
York City. It was the early days of genetic
engineering, and over beers at a guesthouse one
evening, Toenniessen asked a group of plant
breeders how the technology of copying and
pasting genes might benefit rice. "Yellow
endosperm," one of them said.
That odd answer alluded to the fact that a
quarter-billion children have poor diets lacking
in vitamin A. This deficiency can damage the
retina and cornea and increase susceptibility to
measles and other infectious diseases. The World
Health Organization (WHO) estimates that between
250,000 and 500,000 children go blind every year
as a result, and that half of those die within 12
months. Vegetables such as carrots and tomatoes,
as well as meat, butter, and milk, can provide
the vitamin or its precursors, but many families
in poor countries don't have access to them. A
rice variety producing precursors to vitamin A in
its endosperm, the main tissue in seeds, might
provide a solution--and it would have yellow
kernels.

Classical breeding cannot produce such a rice,
however, because although pro-vitamin A is
present in the green parts of the rice plant, no
known strain makes it in its seeds. The only
option is to tinker with rice's DNA to produce
the desired effect. Throughout the 1980s, the
Rockefeller Foundation funded several exploratory
studies, but the plan didn't gel until a
brainstorming meeting in New York City in 1992,
at which scientists discussed the bold idea of
reintroducing the biochemical pathway leading to
beta carotene, the most important pro-vitamin A,
into rice but putting it under control of a
promoter that's specific to endosperm.

Potrykus, then a pioneer in rice transgenics at
the Swiss Federal Institute of Technology (ETH)
in Zürich, attended, as did Beyer, who
specialized in carotenoid biochemistry and
molecular biology. The two met on the plane to
New York and hit it off; their fields of
expertise were complementary, and the fact that
Zürich is less than 2 hours from Freiburg was
helpful. They soon had a proposal written up.

Beyer admits he barely believed in the idea
himself, and the Rockefeller's scientific
advisory board was equally skeptical. Introducing
an entire genetic pathway into rice seemed like a
stretch. Still, the foundation rolled the dice
and supported the project.

It took 7 years, but Potrykus and Beyer
eventually succeeded in making golden rice by
splicing two daffodil genes and a bacterial gene
into the rice genome. The eureka moment arrived
late one night in Freiburg, Beyer recalls. He was
analyzing the molecular content of seeds produced
in Potrykus's lab, as he often did, using a
technique called high-performance liquid
chromatography. This time, peaks showed up on the
screen where they had never appeared before--the
signals of carotenoids. When Beyer went back to
look at the batch of seeds, he noticed something
he had missed: The grains had a faint yellow hue.
Golden rice had been born.

The battle begins
Potrykus says he always knew golden rice--a Thai
businessman suggested the catchy name--would be
controversial. As a professor in Switzerland, one
of the most fiercely anti- GM countries in
Europe, he had been confronted with angry
students since the 1980s. To protect his plants,
ETH spent several million dollars on a
grenade-proof greenhouse. For Beyer, unofficial
road signs declaring the Upper Rhine Valley a "GM
technology-free region" are a twice-daily
reminder that the climate in Germany isn't much
better.

But golden rice posed a special dilemma to GM
crop opponents, admits Benedikt Haerlin, who coordinated
Greenpeace's European campaign at the time and
now works for the Foundation on Future Farming.
Unlike the existing GM crops that primarily
helped farmers and pesticide companies, it was
the first crop designed to help poor consumers in
developing countries. It might save lives. The
decision whether to oppose it weighed heavily on
him, Haerlin says, which is why he consulted with
WHO experts on vitamin A and why he traveled to
Zürich to spend a day at Potrykus's lab to talk.
Potrykus, impressed by Haerlin's intelligence,
hoped to convince his fellow countryman.

He failed. Although Greenpeace pledged not to
sabotage field trials, it did launch an
aggressive campaign against golden rice. It
argued that the crop was an industry PR
ploy--seed company Syngenta was involved in the
project, the group pointed out--designed to win
over a skeptical public and open the door to
other GM crops. Golden rice did not attack the
underlying problem of poverty, Greenpeace said;
besides, other, better solutions to vitamin A
deficiency existed.

Perhaps Greenpeace's most effective argument,
however, was that golden rice simply wouldn't
work. The most successful strain created in 2000
produced 1.6 micrograms of pro-vitamin A per gram
of rice. At that rate, an average 2-year-old
would need to eat 3 kilos of golden rice a day to
reach the recommended daily intake, Greenpeace
said, and a breastfeeding mother more than 6
kilos. To drive the point home, an activist in
the Philippines sat down behind a giant mound of
golden rice during a press conference. "Fool's
gold," Greenpeace called it.

A photo of the event, which quickly found its way
around the world, still makes Haerlin
chuckle--and it still makes Potrykus angry.
Greenpeace assumed that children had to get all
of their vitamin A from rice, which was
unrealistic; it also ignored the fact, says
Potrykus, that even half the recommended intake
may prevent malnutrition. And Greenpeace assumed
that the uptake of beta carotene by the human gut
and its conversion into vitamin A were quite
inefficient, resulting in one vitamin molecule
for every 12 molecules of beta carotene.

Nobody knew the true rate at the time, but a
recent, soon-to-be-published study among healthy
volunteers who ate cooked golden rice, led by
Robert Russell of Tufts University in Boston,
suggests that it's more like one for every three
or four. "That's really quite good," says
Russell, who supports the golden rice project. (A
similar study is planned among people with
marginal vitamin A deficiency in Asia.)
Haerlin says his calculations were based on the
best data at the time. But even if they were
correct, Potrykus says, the first golden rice was
just a proof of principle. Greenpeace might as
well have blamed the Wright brothers for not
building a transatlantic airplane, he says.

Industry gets in
The low beta-carotene yield would eventually be
tackled by Syngenta--even though Potrykus
resented the way the company got involved.
Between 1996 and 1999, Beyer's lab received
funding through a European Commission contract
that also included agrochemical giant Zeneca
(called AstraZeneca after a merger in 1999).
Under the program's rules, any benefits had to be
shared by the signers. AstraZeneca had not worked
on golden rice per se, Potrykus says, but the
company claimed a share of that intellectual
property anyway; it was interested in developing
the technology commercially, for instance in
health foods, says Potrykus, who was initially"furious" that a big corporation now had a say in
his project.

David Lawrence has a different take on those
events: At the time, AstraZeneca primarily wanted
to support the humanitarian development of golden
rice, says the cur rent head of research at
Syngenta; the company didn't have any commercial
plans. (AstraZeneca's agribusiness division
merged with that of Novartis to form Syngenta in
2000.) But whoever's right, the move proved a
blessing in disguise, Potrykus now says. At
Syngenta, he found a new partner in Adrian
Dubock, a bubbly, fast-talking Brit with
experience in patents, product development,
regulation, and marketing--subjects Potrykus and
Beyer admit they were clueless about.

Dubock helped work out a deal in which Syngenta
could develop golden rice commercially, but
farmers in developing countries who make less
than $10,000 a year could get it for free. He
also helped solve patent problems with several
other companies. Dubock retired from Syngenta in
2007 but remains involved as a member of the
Golden Rice Humanitarian Board, a group Potrykus
chairs. "Without him, the project would have
ended already," Potrykus says.

But perhaps most important, Syngenta scientists
replaced a daffodil gene with a maize gene, thus
creating a new version of golden rice, dubbed
GR2, that produces up to 23 times more beta
carotene in its seeds. Even with the one-in-12
conversion factor, that meant 72 grams of dry
rice per day would suffice for a child, the
company's scientists said in 2005. A 2006 paper
by Alexander Stein of the University of Hohenheim
in Stuttgart, Germany, estimated that the rice
could have a major public health impact at a
reasonable cost.

Those results didn't convince the skeptics.
Real-world studies are still lacking, says WHO
malnutrition expert Francesco Branca, noting that
it's unclear how many people will plant, buy, and
eat golden rice. He says giving out supplements,
fortifying existing foods with vitamin A, and
teaching people to grow carrots or certain leafy
vegetables are, for now, more promising ways to
fight the problem.

A golden future?
Today, the debate about golden rice has quieted
down, in part because its inventors are keeping a
low profile. Syngenta stopped its research on
golden rice and licensed the rights to GR2 to the
humanitarian board on World Food Day in 2004;
given consumers' distrust, there was no money in
it, says Lawrence. Most golden rice work is now
taking place at six labs in the Philippines,
India, and Vietnam, the countries chosen as the
best candidates for the crop's launch.

There's a long way to go. Both the original
golden rice, now called GR1, and GR2 were created
with Japonica cultivars that are scientists'
favorites but fare poorly in Asian fields.
Researchers are now backcrossing seven GR1 and
GR2 lines with the long-grained, non-sticky
Indica varieties popular among Asia's farmers. In
early April, researchers at the International
Rice Research Institute in the Philippines
finally started a field trial with a GR1
backcrossed into a widely used Indica variety
called IR64--the first field trial ever in Asia.
(The only other outdoor studies were two done in
Louisiana in 2004 and 2005.) The new varieties
must not only produce enough beta carotene but
also pass muster in terms of yield, seed quality,
and appearance.

The project could have been much further along,
Potrykus says, if there weren't so many rules
governing GM crops that make little sense.
Conventional breeders can bombard plant cells
with chemicals and radiation to create useful
mutants without having to check how it affects
their DNA; a GM insertion must be "clean"--that
is, the extra genes must sit neatly in a row
without disrupting other genes--which adds months
or even years to the lab work. Because field
trials take long to get approved, researchers
have been confined to greenhouses, in which they
have trouble growing the large numbers required
for breeding and feeding studies. These
requirements have caused "year after year of
delays," Potrykus complains.

Even if field trials are successful, there are no
guarantees that golden rice will eventually be
approved in the target countries. Use of other GM
crops, such as Bt cotton, has exploded in Asia in
recent years (see infographic). But GM rice has
languished. In India and China, regulatory
agencies have shied away from approving
insect-resistant GM rice despite extensive
testing. "The expectation is that they will [be
approved] eventually," says Toenniessen, "but
it's a major decision for any Asian country."
Thailand, a major rice exporter, has decided to
steer clear of GM rice altogether.

Kavitha Kuruganti of the Centre for Sustainable
Agriculture, an anti-GM group in Hyderabad,
India, promises a major battle should golden rice
head to the market in India. She thinks that the
crop is unnecessary and probably unsafe to eat
and that a massive switch would reduce diversity
and threaten India's food security. "We will try
to organize a broad public debate," she says.

Not worth funding?
Whether justified or not, the turmoil over golden
rice has shaped other efforts to improve the
nutritional value of crops. Take Harvest- Plus.
With a $14 million annual budget that targets 12
crops, it aims to boost levels of three key
nutrients: vitamin A, iron, and zinc. It relies
almost entirely on conventional breeding--which
has Greenpeace's blessing--because it wants to
have an impact fast, says Bouis, the director.
What little GM technology HarvestPlus supports is
a "hedge," in case the political and regulatory
climates shift.

But in plants that have little or no natural
ability to produce a nutrient, breeders have
nothing to work with. Thus, vitamin A-enriched
non-GM rice and sorghum are essentially off the
table, says Bouis, as is boosting zinc and iron
in sweet potatoes and cassava. Iron in rice is a
question mark.

The uncertainty about the future of GM foods also
tends to scare off the financial donors on which
programs like HarvestPlus depend. Rockefeller,
for instance, is frustrated that a GM rice whose
field trials it helped pay for in China is
stalled, says Toenniessen. "To avoid making the
decision to approve it, the Chinese keep asking
for more field trials," he says. "In the end,
that becomes a foolish use of our funds."

The only charity still investing massively in GM
crops with enhanced nutritional value is the Bill
and Melinda Gates Foundation. Through its Grand
Challenges in Global Health initiative, it is
spending more than $36 million to support not
only golden rice but also GM cassava, sorghum,
and bananas. The foundation declined to comment
for this story. But the researchers it supports
say that they are optimistic that their products
will make it through the pipeline.

James Dale of Queensland University of Technology
in Brisbane, Australia, who heads a project to
add iron, vitamin A, and vitamin E to bananas,
says he has learned several lessons from golden
rice, including the importance of local"ownership"--which is why he has teamed up with
researchers in Kampala. "This will be a Ugandan
banana made by Ugandans," he says.

Not that this mollifies opponents. Greenpeace
will fight to keep GM bananas, cassava, and
sorghum from poor countries' fields, just as it
will keep opposing golden rice, says Janet Cotter
of Greenpeace's Science Unit in London.

Battle-scarred, Potrykus says he hasn't given up
hope that the regulatory system can be overhauled
so that GM technology can benefit the poor. He
believes a massive, multimillion-dollar
information campaign might help convert the
public. He has tried in vain to contact Bill
Gates in hopes of tapping his wealth for such a
media blitz.

He also wrote the late Pope John Paul II to ask
for support for golden rice. "You know the
definition of an optimist?" he jokes: "Someone
who's asking the church for money." His Holiness
declined, but Potrykus was invited to join the
Pontifical Academy of Sciences, where he hopes to
convene a meeting on golden rice next year--the
10th anniversary of his tarnished invention.